This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Traumatic brain injury (TBI) is a leading cause of death and disability in adolescents and young adults and therefore represents a major health problem. Although mild traumatic brain injury (MTBI) is generally nonfatal in this age range, the neurobehavioral effects can persist for months and their mediation by changes in the brain is poorly understood. To gain understanding of changes in brain imaging and neurobehavioral function over three months post-MTBI relative to orthopedic injury (OI), Aim 1 addresses changes in the integrity of cerebral white matter as measured by diffusion tensor imaging (DTI), hemorrhagic lesions seen on susceptibility weighted imaging, and the magnetization transfer ratio on magnetization transfer imaging. Aim 1 also addresses changes in brain region volumes of white matter, gray matter, and cerebrospinal fluid by analysis of magnetic resonance imaging. Aim 1 also investigates the relation of serum biomarkers of MTBI obtained from a blood draw at baseline to the brain imaging variables and whether the concentrations of these biomarkers differentiate MTBI and OI groups. Aim 2 measures change over three months post-injury in MTBI patients relative to the OI group in information processing speed, working memory, episodic memory, and executive functions and the relation of changes in these cognitive domains to brain imaging findings and to functional outcome. Aim 3 measures change over three months in post-concussion symptoms, posttraumatic stress symptoms, emotional status, functional status, and health-related quality of life (HRQL). Aim 3 also studies change in cognitive post-concussion symptoms in relation to brain imaging variables and the relation of change in cognitive, emotional, and somatic post-concussion symptoms to functional outcome and HRQL. We propose a prospective, longitudinal study of 220 right-handed patients, age 14-30 years old, including 88 with MTBI, 44 patients with TBI associated with moderate impairment of consciousness, and 88 patients with OI without brain insult. Selection criteria for the two TBI groups include computed tomography within 24 hours post-injury that shows no brain lesions. All groups would undergo a baseline assessment within 96 hours post-injury, including assessment of pre-injury status, brain imaging, blood draw for surrogate biomarkers, and neurobehavioral testing including cognition, post-concussion and posttraumatic stress symptoms, emotional status, functional status, and HRQL. Brain imaging would be repeated at three months post-injury, and neurobehavioral assessment would be repeated at both one and three months post-injury. Multivariate statistics and the general linear mixed model would be used to analyze the data. By helping to understand the relation of changes in brain imaging to neurobehavioral changes after MTBI in young persons, this studys findings may suggest ways to reduce morbidity and enhance outcomes.